Positron emission tomography (PET) breast imaging can potentially improve the detection and diagnosis of cancer in women with radiodense and/or fibrocystic breasts. Additionally, the quantitative capabilities afforded by PET may also be exploited to provide early and accurate assessment of cancer treatment. During the last four years, our group, with the support of the National Institutes of Health, have developed a high-resolution positron emission mammography and tomography imaging and biopsy device (called PEM-PET) to detect and guide the biopsy of suspicious breast lesions, and quantify radionuclide concentrations in tissue. The system consists of two sets of rotating planar detector heads. Each detector head consists of a 4x3 array of Hamamatsu H8500 flat panel position sensitive photomultipliers (PSPMTs) coupled to a 96W72 array of 2W2W15mm3 LYSO detector elements (pitch= 2.1mm). Image reconstruction is performed with a 3D-OSEM algorithm optimized to run on an eight CPU computer system, significantly reducing image reconstruction times. Initial testing of the device is focusing yielded a spatial resolution at the center of the FOV of 1.87mm (radial), 1.84mm (tangential) and 1.67mm (axial);at 7cm from the center, the results were 1.9mm (radial), 1.89mm (tangential) and 1.69mm (axial). Total system detection sensitivity is 363.3kcps/microcurie/ml. In the continuing development of our breast imaging and biopsy system we propose the further optimization of the PET system;addressing some areas of weakness (count rate performance, for example) identified in our initial testing regime. We also propose the addition of a cone beam, x-ray computed tomography (CT) scanner to the current PEM-PET system, creating the PEM-PET-CT breast imaging and biopsy device. PEM-PET-CT will have the unique ability to continuously rotate during data acquisition, permitting the ability to rapidly produce PET and CT images. The anatomical information gained by integration of the CT imager will permit the correlation of structural features of the breast and abnormal areas with functional information from these areas. Thus, the two methods complement each other well. The data provided by the CT images will also be used improve corrections for physical phenomena that can confound quantitative measures of radiotracer concentrations. Finally, the completed system be tested in these two application during a pilot human trial, comparing its performance to whole body PET, MRI and MRS. The data from these studies will be crucial in the planning of future larger human trials. We envision that PEM-PET-CT could be used to detect lesions in women with dense breasts and indeterminate mammograms that have additional risks factors for cancer. It could also be used in the diagnostic role as a "second look" method to assess suspicious lesions or micro- calcifications. Lastly, the unique quantitative capabilities of the system could facilitate its use in treatment assessment of chemotherapy, especially in small tumors. Thus, the development of this new multi-modality system is a unique opportunity to improve a number of important clinical aspects of breast care. PUBLIC HEALTH RELEVANCE This application proposes the continued development of a dedicated breast PET-CT system. This device could be instrumental in the detection, diagnosis and treatment assessment of breast cancer.